Niraparib for Advanced Ovarian Cancer with HRD+ Status Approved by FDA

Niraparib was approved by the (FDA) for previously treated advanced ovarian, fallopian, or primary peritoneal cancers.

Niraparib (Zejula) was approved by the US Food and Drug Administration (FDA) today for previously treated advanced ovarian, fallopian, or primary peritoneal cancers. The approval was specifically for cancer previously treated with three or more chemotherapy regimens, and which is also homologous recombination deficiency (HRD)-positive. 

The approval of the drug is based on the single-arm QUADRA study, part of the results of which were published in The Lancet Oncology in May. The QUADRA study concluded that it was not only patients with BRCA mutation, but those without the genetic mutation, who could benefit. 

“Our data support expansion of the treatment indication of poly (ADP-ribose) polymerase inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutation,” the investigators wrote at the time.   

The FDA cited data from part of the QUADRA study focusing on 98 patients who had HRD-positive tumors, who had undergone 3 or greater prior chemotherapy lines. All the patients received 300 mg niraparib orally once daily, until there was disease progression or unacceptable toxicity. 

The overall response rate (ORR) and duration of response (DOR) were the primary objectives. The findings showed: ORR at 24% (95% CI: 16,34) and DOR at 83 months (95% CI: 6.5, not able to be estimated).

Among the tumor BRCA-mutated (tBRCAm) subset, ORR was 39% (7 of 18 patients; 95% CI; 17, 64) in those with platinum-sensitive disease; 29% (6 of 21; 95% CI: 11,52) for platinum-resistant disease; and 19% for platinum-refractory disease (3 of 16; 95% CI: 4,46).

However, a majority of patients had dose reduction or interruption due to adverse reactions. A total of 73% of the QUADRA group had some alteration to the regimen, due to thrombocytopenia (40%), anemia (21%), nausea (13%), neutropenia (11%), vomiting (11%), fatigue (9%), and abdominal pain (5%), according to the FDA statistics. 

The overall results of the phase II QUADRA trials encompassed 463 enrolled patients between 2015 and 2018. 


Earlier this month, the FDA granted breakthrough therapy designation to niraparib for the treatment of men with BRCA1/2-mutant positive metastatic castration-resistant prostate cancer (mCRPC) who previously received taxane-based chemotherapy and an androgen receptor (AR) inhibitor, according to Janssen, the drug’s developer.


Moore K, Secord A, Geller M, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):636-648. doi: 10.1016/S1470-2045(19)30029-4. Epub 2019 Apr 1.